Breast cancer cell defects linked with lymph node metastases

Breast tumors that carry breast cancer stem and progenitor cells (BCSCs) with mutations in specific oncogenes are significantly more likely than other breast cancers to metastasize to the lymph nodes, researchers reported.

Mutations in oncogenes AKT1, HRAS, and PIK3CA result in abnormal P13K/Akt signaling and tumor proliferation, explained Cory A. Donovan, MD, of the division of surgical oncology at Oregon Health & Science University, Portland, Oregon, and colleagues in JAMA Surgery. These mutations occur in ductal carcinoma in situ, breast cancers, and BCSCs.

The investigators sought to determine whether variability in clinical presentation at diagnosis correlates with PI3K/Akt mutations in BCSCs and provides an early prognostic indicator of increased progression and metastatic potential. They collected malignant BCSCs and benign stem cells from fresh surgical specimens, and tested for oncogene mutations from 30 invasive ductal breast cancers (stages IA through IIIB).

Donovan and associates found that 10 tumors had mutations in their BCSCs. In total, nine tumors with BCSC mutations and four tumors with BCSCs without mutations had associated tumor present in the lymph nodes.

The mutated BCSCs were markers of more aggressive breast cancer, yet these oncogenic defects may be missed by gross molecular testing of the tumor. Donovan's team suggested that molecular profiling of BCSCs may identify patients who would likely benefit from PI3k/Akt inhibitors, which are being tested in clinical trials.
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